Modafinil

PEP Topic

Cognitive Impairment

Description

Modafinil is a psychostimulant that is effective in the treatment of excessive sleepiness associated with narcolepsy and in persons with shift-work sleep disorder (Blackwell et al., 2009). It is used to brigthen the mood and enhance wakefulness, memory, and attention capacity. Modafinil comes as a tablet for oral intake, and has been evaluated in patients with cancer for fatigue and cognitive impairment.

Study Purpose:

The study's primary aim was to evaluate the safety and efficacy of modafinil in improving cancer-related fatigue. Its secondary aim was to determine the effect of modafinil on depression, quality of life, functional status, and cognitive function.

Intervention Characteristics/Basic Study Process:

Participants were given 100 mg of modafinil daily for weeks 1 and 2, and then 200 mg daily for weeks 3 and 4. Participants older than 80 were dose-reduced and received 50 mg of modafinil daily for weeks 1 and 2, then 100 mg daily for weeks 3 and 4. There was no control group.

Testing was completed at baseline, week 2, and at the completion of the trial.

Sample Characteristics:

The total number of participants was 27, with 19 completing the study.

The average participant age was 60 years.

63% of participants were female and 37% were male.

37% of participants had an Eastern Cooperative Oncology Group (ECOG) score of 1, 44% had a score of 2, and 19% had a score of 3.

The National Cancer Institute Common Toxicity Criteria (CTC), Version 2.0 scored the severity of detected side effects.

Results:

Fatigue (as measured by the BFI) was improved at week 2 for 46% of participants; at week 4, 75% had a significantly improved score (p = 0.025). Functioning (as measured by the FACT-BR) showed an improvement in all subsets of well-being at weeks 2 and 4 (p < 0.05) except social/family. Depression (as measured by the HADS) declined significantly at weeks 2 and 4 (p < 0.001).

Functional status (as measured by the Barthel Index) did not change, but overall ECOG performance status improved, with 40% of patients improving at least one level. Cognitive function was not significantly changed, although the TMT-B did show a trend of overall improvement.

Conclusions:

Modafinil did not significantly improve learning and memory, fine motor ability, verbal fluency, or executive function, but results are limited due to the small sample size.

Limitations:

This was a pilot study addressing fatigue, with cognitive function measured as a secondary outcome.

The study had a small number of participants, with a drop-out ratio of 30%.

The study had an open-label design.

There was no control group.

Results for improvement on the TMT-B may be due to Type I error, given the multiple tests (multiple comparisons) examined in this trial.

The study had limited cognitive assessment.

The issue of practice effects was not addressed in a repeated measures study.

Study Purpose:

The study's primary aim was to examine the effect of modafinil on persistent fatigue after treatment. Its secondary aim was to examine the effect of modafinil on cognitive function of patients with breast cancer.

Intervention Characteristics/Basic Study Process:

In phase 1, participants were given 200 mg of modafinil daily for four weeks. Participants with a positive response in phase 1 were randomized to phase 2. In phase 2, participants continued to receive 200 mg of modafinil orally once per day or a placebo for four weeks. Repeated measures were completed at baseline (week 0), week 4, and week 8. Participants were stratified by treatment type: chemotherapy, radiation, or both chemotherapy and radiation.

Sample Characteristics:

The total number of participants was 82, with 76 completing phase 1 and 68 completing phases 1 and 2.

The median participant age was 54, with a range of 33–83.

All participants were female.

All participants had breast cancer and were being treated with surgery and chemotherapy; 87% also received radiation.

75% of participants had at least some college education.

Setting:

The study took place at the University of Rochester Medical Oncology Clinic in New York.

Study Design:

The study was a prospective, open-label clinical trial.

Measurement Instruments/Methods:

The Cognitive Drug Research (CDR) assesses domains of attention and memory, including speed of memory, continuity of attention, quality of episodic and working memory, and power of attention.

The Brief Fatigue Inventory (BFI) assess fatigue.

Results:

Approximately 70% of the participants in the active treatment group had an improvement in continuity of attention from baseline to after treatment (week 8), compared with 52% in the placebo group; however, this difference was not statistically significant (p = 0.19).

In phase 1, modafinil had a significant effect on speed of memory (p = 0.0073) and quality of episodic memory (p = 0.0001). No significant effect in continuity of attention, quality of working memory, or power of attention was observed during this phase.

Study Purpose:

The study's primary aim was to assess the effectiveness of single-dose modafinil on cognitive function in patients with advanced cancer treated in palliative care settings. Its secondary aim was to assess the effectiveness of modafinil on other symptoms.

Intervention Characteristics/Basic Study Process:

On day 1, patients were randomly assigned to receive either 200 mg of modafinil or an oral placebo. On day 4, each patient group was given the alternative treatment that was not dispensed on day 1.

Sample Characteristics:

The number of participants was 28.

The median participant age was 62, with a range of 40–79.

57% of the participants were male and 43% were female.

All participants had advanced cancer, with a variety of hematologic and solid tumors.

All participants had a tiredness score fo 50 mm on the Edmonton System Assessment Scale and a score range of 40–70 on the Karnofsky Performance Status Scale.

Setting:

The study took place in the palliative care department of Herning Hospital in Denmark.

Study Design:

The study was a double-blind, randomized, cross-over, single-dose trial.

Measurement Instruments/Methods:

The Finger Tapping Test (FTT) is well-validated test of psychomotor speed that is used for detecting lateral cerebral lesions and unspecific psychomotor impairment.

The Trail Making Test, Part B (TMT-B) is a test of visual information processing used to assess visual search skills, scanning, speed of processing, mental flexibility, attention, and psychomotor speed.

The Karnofsky Performance Status Scale measures general well-being. Scores range from 0 (death) to 100 (perfect health with no complaints or signs of disease).

Results:

Patients on the modafinil treatment group saw statistically significant improvements in psychomotor speed with the dominant hand (as measured by the FTT) and speed of processing (as measured by the TMT-B), as compared with the placebo group (p = 0.006). The modafinil treatment group also showed statistically significant improvements in depression and drowsiness as compared with the placebo group (p = 0.042).

The frequency and intensity of side effects were similar on both treatments, and no statistically significant differences were reported. However, four patients experienced disrupted sleep and vivid dreams after modafinil treatment.

Conclusions:

Limitations:

The number of participants was small, but was in congruence with priori power analyses.

The study design had limited administration of the medication (only one single dose) and follow-up; therefore, no conclusions can be made about long-term usage of modafinil.

The authors reported that patients were allowed to use supplemental doses of short-acting opioids for breakthrough pain throughout the study, except before testing on study days. The holding of as-needed opioids is an ethical concern for patient comfort. Although opioid use was controlled, patients may have been in pain, which would confound cognitive results.

No information regarding pain prior to cognitive testing was noted.

The authors did not address practice effects with repeated administration of the TMT-B.